Continuous DOT Imaging of Hemodynamics During Stroke" is submitted in response to the NINDS program announcement for Mentored Quantitative Research Career Awards (K25). The candidate seeks to gain training in the neurobiology of Stroke and to advance the methods of Diffuse Optical Tomography (DOT) for application in stroke physiology. Stroke is both caused by, and induces deranged hemodynamics. It is therefore not surprising that the hemodynamic status of ischemic tissue contains vital and abundant information about microvasculature integrity, deficient cerebral metabolism, and abnormal neuronal activity. Diffuse optical imaging of the brain is an attractive approach for evaluating stroke physiology. The method provides complementary hemodynamic and metabolic imaging contrasts to those of Magnetic Resonance Imaging (MRI) with a unique potential for continuous non-invasive bedside imaging in humans. However quantitative spatial-temporal, comparative studies with established medical imaging techniques are lacking. In addition, experience with diffuse optical signatures of stroke pathophysiology is limited, and mostly involves non-imaging measures. The goal of this work is to establish new DOT hemodynamic and metabolic methodologies through concurrent DOT-N4RI animal (rat) studies, and apply the methods to examine the spatial-temporal evolution of reperfusion and hemorrhagic transformation with thrombolytics. The new DOT techniques are based on NEU guided Monte-Carlo diffuse light modeling, and hybrid time resolved and continuous-wave light measurements. Methods for quantifying and imaging cerebral blood volume (CBV), cerebral blood flow (CBF), and indexes of cerebral oxygen metabolism (CMRO) will be validated through global and focal programmed modulations of cerebral vasculature and physiology. Subsequent studies will explore DOT markers relevant to focal ischemia, thrombolytics, and hemorrhage due to reperfusion. Through the training that this award provides the applicant will gain sufficient background in the neuroscience and cerebral ischemia to lead cross-disciplinary research projects that aim to further the knowledge of stroke physiology.